In hemoglobin, the innate affinity of heme for carbon monoxide is diminished by the presence of -

Isolated heme binds carbon monoxide (CO) 25,000 times more strongly than oxygen. However, in myoglobin and hemoglobin, heme binds carbon monoxide to only about 200 times more strongly than oxygen. This is because of distal histidine (His E7 of protein part of hemoglobin and myoglobin create a hindered environment which precludes the high-affinity orientation of CO. The details of this mechanism are not required at this level.